The basement membrane is a ubiquitous, specialized type of extracellular matrix separating organ parenchymal cells from interstitial collagenous stroma. Interaction of cells with this matrix is an important aspect of both normal and neoplastic cellular processes. Normal cells appear to require an extracellular matrix for survival, proliferation, and differentiation, while migratory cells, both normal and neoplastic, must traverse the basement membrane in moving from one tissue to another. In particular, metastatic cancer cells arising in squamous or glandular epithelium must traverse the basement membrane to enter the circulatory and lymphatic systems (intravasation); the circulating neoplastic cells are typically arrested in the capillary beds of an organ, invade the blood vessel walls, and penetrate the basement membrane to extravascular tissue (extravasation), where a secondary neoplasm is then established. The mechanisms of cellular interaction with the basement membrane are thus of great interest.
The interaction of cells with extracellular matrices is dependent upon the ability of the cells to attach themselves to the matrix; it is known that this attachment may be mediated by specific glycoproteins which typically bind cells to discrete collagen types present in the matrix. Fibronectin-mediated attachment of fibroblasts, myoblasts, and smooth muscle cells to intersititial type I and type III collagen, and chondronectin-mediated attachment of chondrocytes to type II cartilage collagen, are exemplary.
It has been found that the attachment of both normal and neoplastic cells to the basement membranes is similarly mediated. The primary constituents of the basement membrane are type IV collagen, glycoproteins. and proteoglycans. The glycoprotein laminin mediates the attachment of both epithelial and neoplastic calls to the basement membrane, binding the cells to type IV collagen by mechanisms to be described hereinafter. Since, as previously noted, metastasizing tumor cells must traverse basement membranes at multiple stages in the metastatic process, and since the first step in this process is tumor cell attachment to the basement membrane, the elucidation of this mechanism and the corollary characterization of specific attachment factors which promote or inhibit tumor cell attachment to this membrane has important implications for cancer diagnosis and management.